NM_000038.6(APC):c.7550A>G (p.Tyr2517Cys) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 16, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000759443.15

Allele description [Variation Report for NM_000038.6(APC):c.7550A>G (p.Tyr2517Cys)]

NM_000038.6(APC):c.7550A>G (p.Tyr2517Cys)

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.7550A>G (p.Tyr2517Cys)

HGVS:

NC_000005.10:g.112843144A>G
NG_008481.4:g.155624A>G
NM_000038.6:c.7550A>GMANE SELECT
NM_001127510.3:c.7550A>G
NM_001127511.3:c.7496A>G
NM_001354895.2:c.7550A>G
NM_001354896.2:c.7604A>G
NM_001354897.2:c.7580A>G
NM_001354898.2:c.7475A>G
NM_001354899.2:c.7466A>G
NM_001354900.2:c.7427A>G
NM_001354901.2:c.7373A>G
NM_001354902.2:c.7277A>G
NM_001354903.2:c.7247A>G
NM_001354904.2:c.7172A>G
NM_001354905.2:c.7070A>G
NM_001354906.2:c.6701A>G
NP_000029.2:p.Tyr2517Cys
NP_001120982.1:p.Tyr2517Cys
NP_001120983.2:p.Tyr2499Cys
NP_001341824.1:p.Tyr2517Cys
NP_001341825.1:p.Tyr2535Cys
NP_001341826.1:p.Tyr2527Cys
NP_001341827.1:p.Tyr2492Cys
NP_001341828.1:p.Tyr2489Cys
NP_001341829.1:p.Tyr2476Cys
NP_001341830.1:p.Tyr2458Cys
NP_001341831.1:p.Tyr2426Cys
NP_001341832.1:p.Tyr2416Cys
NP_001341833.1:p.Tyr2391Cys
NP_001341834.1:p.Tyr2357Cys
NP_001341835.1:p.Tyr2234Cys
LRG_130t1:c.7550A>G
LRG_130:g.155624A>G
NC_000005.9:g.112178841A>G
NM_000038.4:c.7550A>G
NM_000038.5:c.7550A>G

Protein change:

Y2234C

Links:

dbSNP: rs587783036

NCBI 1000 Genomes Browser:

rs587783036

Molecular consequence:

NM_000038.6:c.7550A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.7550A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.7496A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.7550A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.7604A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.7580A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.7475A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.7466A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.7427A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.7373A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.7277A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.7247A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.7172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.7070A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.6701A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000566783	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jan 3, 2024)	germline	clinical testing	Citation Link,
SCV000888765	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (May 16, 2024)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 33606809, 30102335, 26580448, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000566783

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jan 3, 2024)

germline

clinical testing

Citation Link,

SCV000888765

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(May 16, 2024)

unknown

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline molecular data in hereditary breast cancer in Brazil: Lessons from a large single-center analysis.

Sandoval RL, Leite ACR, Barbalho DM, Assad DX, Barroso R, Polidorio N, Dos Anjos CH, de Miranda AD, Ferreira ACSM, Fernandes GDS, Achatz MI.

PLoS One. 2021;16(2):e0247363. doi: 10.1371/journal.pone.0247363.

PubMed [citation]

PMID:: 33606809
PMCID:: PMC7895369

CharGer: clinical Characterization of Germline variants.

Scott AD, Huang KL, Weerasinghe A, Mashl RJ, Gao Q, Martins Rodrigues F, Wyczalkowski MA, Ding L.

Bioinformatics. 2019 Mar 1;35(5):865-867. doi: 10.1093/bioinformatics/bty649.

PubMed [citation]

PMID:: 30102335
PMCID:: PMC6394391

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000566783.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast cancer or leukemia (PMID: 33606809, 30102335, 26580448); This variant is associated with the following publications: (PMID: 30102335, 33606809, 26580448)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000888765.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The APC c.7550A>G (p.Tyr2517Cys) variant has been reported in the published literature in an individual with breast cancer (PMID: 33606809 (2021)), as well as in an infant with acute lymphoblastic leukemia (PMIDs: 30102335 (2019) and 26580448 (2015)). The frequency of this variant in the general population, 0.00012 (4/34578 chromosomes in Admixed American subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 19, 2025

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